Periodic Reporting for period 1 - SMs-Gut (Functional characterization of specialized metabolites from gut microbiomes)
Reporting period: 2020-11-01 to 2022-10-31
Gut-related diseases, such as CRC and IBC, pose significant health threats to mankind. Yet the mechanisms for their development and progression are still not well understood. In particular, the potential role of the gut microbiota and their specialized metabolism in this context is fully unclear. Understanding the impact of the interaction of gut microbiota and host in the context of disease is crucial to develop better preventive measures and treatment options and thus has the potential to help solve important medical questions. Within this project, novel methods for the targeted discovery, production, and functional study of specialized gut metabolism have been developed. These tools are important to enable future systematic studies on gut health and disease.
The performed work included the bioinformatic mapping of the biosynthetic potential of selected members of human and mouse gut microbiota, the development of new cloning techniques for the interception of biosynthetic pathways, the heterologous expression of such pathways in E. coli, and the isolation of the respective small molecule products, in addition to the functional characterization of the latter in the context of human diseases development. This led, i.a. to the discovery of yet unknown selective cytotoxins produced by a gut bacterium that might play a role in CRC development of progression. The results of this work are currently being processed for publication.
The project provides a new approach for the direct cloning of large (>25 kb) biosynthetic pathways for recombinant production of small molecules. In addition, yet unknown deleterious effects of small molecules produced by gut microbiota have been identified. These findings will help develop streamlined platforms for small molecular discovery from the gut and beyond and have the potential to help develop novel approaches for the diagnosis of CRC-promoting factors and for the treatment of gut diseases.